It is generally believed that all biological functions can be interpreted on a molecular level and that there exists a structure-function relationship. Optical rotatory dispersion (ORD) and circular dichroism (CD) have now been widely used in studying the conformation of biopolymers in solution. We have recently developed a method of analysis (BIOCHEMISTRY 11, 4120 (1972)), which allows us to determine the percentages in helix and beta-form in a protein molecule. One of our objectives will be to study the relative change in helix and B-form that accompanies denaturation by heat, chemical reagents, or changes in pH. Proteins of known structure will be studied first. Biological activities at each stage of denaturation will be correlated with the secondary structure of the protein molecule. Second, we will continue to explore the applications, improvements and limitations of the ORD and CD techniques. Attempts will be made to resolve the optical activity of non-peptide chromophores from that of peptide conformation. Third, the influence of side chains on the stability of polypeptide conformation will be further investigated through the syntheses of polypeptide homologs and their characterization by ORD and CD and other physical methods. Fourth, the effect of detergents on protein conformation will be systematically studied with the use of homogeneous (as distinguished from commercial mixtures) detergents specifically synthesized for this purpose. Our objective is to gain a better understanding of the hydrophobic interaction of these detergents with respect to protein conformation.